3C
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Clinical Question
In adult patients with lower respiratory tract infections without evidence of pneumonia, how does the administration, timing or lack of antibiotics correlate to reconsultation for non-resolving symptoms, hospital admission, or death?
Bottom Line
For uncomplicated lower respiratory tract infections (LRTI) without evidence of pneumonia, delayed antibiotics may decrease the rate of reconsultation for non-resolving symptoms, and either immediate or delayed antibiotics may not reduce the rates of hospital admission or death.
Major Points
Antibiotics have not demonstrated clear benefit when administered for acute, uncomplicated (e.g., no pneumonia or lung abscess), ambulatory, community based lower respiratory tract infections, in clinical trials[1] or in a Cochrane review.[2]
The Cough Complication Cohort (3C) study was a prospective, observational cohort study conducted in 522 primary care facilities in the UK. The study included 28,779 patients with uncomplicated illness seen for initial outpatient consultation, of whom 25.5% received no prescription for antibiotics, 61.3% received a prescription for antibiotics to begin immediately, and 13% received a prescription for antibiotics to be taken if symptoms worsen. Patients' outcomes were assessed via review of clinical documentation at 30 days after the initial consultation. The primary outcomes were reconsultation (repeat visit at a primary care office or emergency department), hospitalization, or death. Reconsultation occurred in 19.7% in the no antibiotics group, 25.3% in the immediate antibiotics group, and 14.1% in the delayed antibiotics group, with a significant reduction in the number of reconsultations in the delayed antibiotics group (HR 0.64, P<0.01) but not in the immediate antibiotics group (HR 0.98, P=0.97). Rates of hospitalization or death were <1% in all groups. The investigators used various methods to address confounding, but acknowledge that the non-randomized study design carries limitations. Ultimately the authors conclude that a delayed antibiotic strategy may reduce rates of reconsultation in patients with uncomplicated lower respiratory tract infections.
Guidelines
As of September 2019, no guidelines have been published that reflect the results of this trial.
Design
- Prospective, observational cohort study
- N=28,779 outpatient adults with uncomplicated lower respiratory tract illness
- No antibiotics (n=7,332; 25.4%)
- Immediate antibiotics (n=17,628; 61.3%)
- Delayed antibiotics (n=3,819; 13.3%)
- Setting: 522 UK primary care facilities
- Enrollment: October 2009–April 2013
- Follow-up: 30 days
- Primary endpoint: Reconsultation, hospitalization, or death
Population
Inclusion Criteria
- Age ≥16 years
- Acute lower respiratory tract infection with an acute infected cough as the main symptom (acute infected cough defined as a cough new or worsening for ≤3 weeks)
Exclusion Criteria
- Other causes of acute cough (eg, heart failure, acid reflux, fibrosing alveolitis, cancer)
- Immunocompromised
- Previous episodes of the same illness
- Previous inclusion
- Admission to hospital on day of index consultation
- Confirmed pneumonia on radiography
- Inability to consent
Baseline Characteristics
| Characteristic | No antibiotics | Immediate | Delayed |
|---|---|---|---|
| Age ≥60 years | 28.8% | 42.3% | 33.4% |
| Female | 60.7% | 58.6% | 59.8% |
| Illness duration <7 days | 47.7% | 50.2% | 42.1% |
| Pneumovax within 10 years | 14.1% | 20.7% | 15.7% |
| Ever smoker | 49.4% | 56.0% | 49.2% |
| Comorbidities | 36.8% | 49.8% | 41.4% |
| Lung comorbidity | 20.1% | 29.0% | 22.4% |
| Taking steroids or bronchodilators | 17.9% | 26.9% | 20.2% |
| Deprived area | 20.3% | 20.4% | 17.1% |
| Symptoms | |||
| Dyspnea | 52.9% | 70.2% | 59.6% |
| Fever | 29.2% | 42.0% | 37.7% |
| Purulent sputum | 49.0% | 68.8% | 64.4% |
| Examination | |||
| Severity assessment ≥5/10 | 11.5% | 56.3% | 28.6% |
| Respirations >24/min | 6.0% | 12.3% | 6.9% |
| Temperature ≥37.8ºC | 2.7% | 7.4% | 3.9% |
| Pulse ≥100/min | 6.6% | 11.5% | 7.5% |
| O2 saturation <95% | 2.7% | 9.8% | 3.8% |
| SBP <90 or DBP <60 mm Hg | 8.7% | 7.4% | 6.5% |
| Crackles | 2.4% | 63.7% | 21.3% |
| Wheeze | 8.0% | 33.5% | 14.5% |
Interventions
This was a non-interventional, prospective, cohort study. The investigators used propensity score matching to attempt to account for confounding.
Outcomes
Note, the presented comparisons include propensity score-matched risk ratios (RR) to account for bias. The percentages are included for completeness' sake. Comparing the percentages of the outcomes in each group directly does not account for bias.
Primary Outcomes
- Hospital admission or death after uncomplicated presentation within 30 days
- No antibiotics 0.3%
- Immediate antibiotics 0.9% (RR 1.06; 95% CI 0.63-1.81; P=0.84)
- Delayed antibiotics 0.4% (RR 0.81; 95% CI 0.41-1.64; P=0.61)
Secondary Outcomes
- Reconsultation with non-resolving or worsening symptoms within 30 days
- No antibiotics 19.7%
- Immediate antibiotics 25.3% (RR 0.98; 95% CI 0.90-1.07; P=0.97)
- Delayed antibiotics 14.1% (RR 0.64; 95% CI 0.57-0.72; P<0.01)
Criticisms
- There was no training for or mechanism to ensure quality of the diagnostic skills used by the physicians
- Bias potentially occurred due to missing oxygen saturation data
- Patients included in the trial were not blind to their antibiotic therapy or lack there of therapy
- Patients were recruited during the busiest part of the year
- Patients not approached for consent were not documented
- Trial powered only for detecting odds ratio greater than 0.66
- Did not describe the antimicrobial regiment utilized
Funding
- Grant for independent research from the National Institute for Health Research (NIHR)
Further Reading
- ↑ Little P et al. Effects of internet-based training on antibiotic prescribing rates for acute respiratory-tract infections: a multinational, cluster, randomised, factorial, controlled trial. Lancet 2013. 382:1175-82.
- ↑ Smith SM et al. Antibiotics for acute bronchitis. Cochrane Database Syst Rev 2014. :CD000245.